Advanced solid tumors and multiple myeloma MedDRA version: 16.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864 MedDRA version: 16.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: TAS-120
Product Code: TAS-120
Pharmaceutical Form: Capsule
INN or Proposed INN: Not yet assigned
CAS Number: 1448169-71-8
Current Sponsor code: TAS-120, TAS-06-02985
Other descriptive na
Sponsors
Taiho Pharma USA, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent. 2. Age of 18 years or over. 3. Phase 1 Dose Escalation: Patients with histologically or cytologically confirmed advanced, measurable or non-measurable (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] guidelines [version 1.1, 2009]) metastatic solid tumor(s) who have failed all standard therapies or for whom standard therapy does not exist. Starting with Dose Level 5 of each dosing schedule, only patients with locally diagnosed amplification, mutation, translocation or other associated abnormalities of FGF/FGFR will be enrolled (see Section 8.12, Pharmacogenomic (FGF/FGFR) Analysis). 6. Able to take medications orally (eg, no feeding tube). 7. Adequate organ function as defined by the following criteria: a. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 1 500/mm3 (ie, >= 1.5 × 109/L by International Units [IU]) (excluding measurements obtained within 7 days after administration of granulocyte colony-stimulating factor [G-CSF]). d. Platelet count >= 100 000/mm3 (IU: >= 100 × 109/L) (excluding measurements obtained within 7 days after a transfusion of platelets). e. Hemoglobin >= 8.0 g/dL (excluding measurements within 4 weeks of a transfusion of packed red blood cells [RBCs] or whole blood). f. Serum Phosphorus = 1 g/dL of monoclonal protein in serum. ? Urine protein electrophoresis (UPEP) > 200 mg of monoclonal protein in urine (based on 24-hour urine). ? Serum free light chain (SFLC): involved free light chain (FLC) >= 10 mg/dL (>= 100 mg/L) AND abnormal kappa to lambda SFLC ratio. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 335
Exclusion criteria
Exclusion criteria: 1. History and/or current evidence of endocrine alteration of calcium-phosphorus homeostasis. 2. History and/or current evidence of ectopic mineralization/calcification including but not limited to soft tissue, kidneys, intestine, or myocardia and lung with the exception of calcified lymph nodes and asymptomatic arterial calcification. 3. Current evidence of corneal disorder/keratopathy including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjuctivitis, etc, confirmed by ophthalmologic examination. 5.QTc > 470 msec on ECG conducted during Screening period 6. Treatment with any of the following within the specified time frame prior to the first dose of TAS-120: a. Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of TAS-120). b. Radiotherapy for extended field within 4 weeks prior to the first dose of TAS-120 or limited field radiotherapy within 2 weeks prior to the first dose of TAS-120. c. Any noninvestigational anticancer therapy within 3 weeks prior to TAS-120 administration (mitomycin within prior 5 weeks). d. Any medication administered within 7 days prior to first dose of TAS-120 that is known to affect QT interval or to be arrhythmogenic such as, but not limited to, the following drugs (http://creciblemeds.org/pdftemp/pdf/CompositeList.pdf): i. Ondansetron ii. Erythromycin iii.Droperidol iv. Halofantrine e. Any investigational agent received either concurrently or within the previous 30 days. 7. A serious illness or medical condition(s) including, but not limited to, the following: a. Known brain metastasis unless patient is clinically stable and off corticosteroids for >= 2 months. b. Known leptomeningeal metastasis. c. Known acute systemic infection. d. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV (see Appendix B, New York Heart Association [NYHA] Classification) within the previous 6 months; if > 6 months cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms. e. Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the investigator. f. Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness, or a history of serum positivity to hepatitis B or C. g. Congenital long QT syndrome, or any known history of torsade de pointes (TdP), or family history of unexplained sudden death. h. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or TAS-120 administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study. 8. Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 Dose Escalation: To investigate the safety and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of TAS 120 and its associated dosing schedule in patients with advanced solid tumors with or without FGF/FGFR abnormalities who have failed all standard therapies or for whom standard therapy does not exist. Phase 1 Expansion and Phase 2: To investigate the efficacy of the TAS 120 RP2D in patients with NSCLC, breast, gastric, and other solid tumors or multiple myeloma, with FGF/FGFR abnormalities for whom no available therapy is likely to convey clinical benefit.;Secondary Objective: Phase 1 Dose Escalation: ? To investigate the clinical pharmacokinetics (PK) of TAS-120. ? To investigate the clinical pharmacodynamics of TAS-120. ? To determine any preliminary antitumor activity observed with TAS-120. Phase 1 Expansion and Phase 2: ? To investigate the safety of TAS-120.;Primary end point(s): The primary endpoint in phase 1 expansion and phase 2 of the study is overall response rate (ORR). Overall response rate is defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR). Endpoint for Phase 1 dose escalation is determination of maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D).;Timepoint(s) of evaluation of this end point: The endpoint is based on Overall response rate (ORR). For multiple myeloma, this includes ? partial response (PR) as defined by IMWG criteria. In order to be classified as a response, confirmation of serum monoclonal protein, serum immunoglobulin FLC (when primary determinant of response), and urine monoclonal protein (when primary determinant of response) results must be made by verification on 2 consecutive determinations, which is every 3 weeks (Day 1 of each cycle). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints in Phase 1 dose escalation are pharmacokinetic and pharmacodynamic parameters. Secondary endpoints in Phase 1 Expansion and Phase 2 are disease control rate (DCR) and duration of response (DR) in both phases. DCR is defined as the proportion of patients with objective evidence of Complete Response, Partial Response or Stable Disease. Duration of response is defined as the time from the first documentation of response to the first documentation of objective tumor progression or death due to any cause;Timepoint(s) of evaluation of this end point: The timepoints for assessment will parallel that for the primary endpoint. | — |
Countries
Australia, France, Germany, Netherlands, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactManuel Aivado
Taiho Pharma USA, Inc.
Outcome results
None listed